EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.
EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.
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EGF 和 HB-EGF 调节正常和间质性膀胱炎患者膀胱尿路上皮细胞的内向钾电流。
DOI：
10.1152/ajpcell.00209.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Chai,TobyC
中科院分区：
文献类型：
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作者：
Sun,Yan;Chen,Mingkui;Lowentritt,BenjaminH;VanZijl,PSean;Koch,KristopherR;Keay,Susan;Simard,JMarc;Chai,TobyC
间质性膀胱炎(IC)是一种以膀胱痛觉过敏为特征的特发性疾病。研究表明，IC患者培养的膀胱尿路上皮细胞(BUC)存在细胞因子和嘌呤能信号异常。我们在正常和IC BUC中进行了单细胞电生理研究。在正常BUC中发现了一种具有Kir2.1通道电导的强内向整流钾电流。这种电流在IC BUC中显著降低。Kir2.1蛋白和mRNA在IC和正常BUC中均有表达。表皮生长因子(EGF)使正常BUC的内向钾电流呈剂量依赖性下降。IC BUC分泌较高数量的EGF，并且已知通过对Kir2.1的磷酸化来降低Kir2.1的电导。非特异性磷酸化抑制剂金雀异黄素可增加IC BUC的内向钾电流，并阻断EGF对正常BUC的作用。用肝素结合的表皮生长因子样生长因子(HB-EGF)治疗IC BUC，可显著增加内向钾电流。这些数据表明，BUC的内向钾电流可被EGF和HB-EGF所调制。因此，EGF和HB-EGF水平改变引起的BUC膜钾电导的改变可能在IC的病理生理过程中起一定作用。
Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.